Fibroblast Cells Physiological Changes

Several lines of evidence suggest that senescent cells, including fibroblasts, exist and accumulate with age in at least some mammalian tissues in vivo. First, progressive telomere shortening, a hallmark of replicatively senescent human cells, occurs in some human tissues and cells (e.g., segments of the aorta and T lymphocytes) with increasing age. Second, some—but not all—studies show that fibroblasts from older donors have shorter replicative life spans than fibroblasts from younger donors. The discrepancy among studies may be due to genetic variation among individual donors or, more likely, the variation within even a single tissue in replicative history of the small regions that are sampled in biopsies. Indeed, there is substantial scatter in the data from even the most convincing studies showing an inverse correlation between donor age and replicative life span of fibroblasts from skin biopsies. That is, in all the studies, there are some cultures from young donors that senesce quickly, and some cultures from old donors that proliferate for many doublings. Third, in the mid-1990s a marker enzyme was described that increased when cells were induced to senesce by a variety of stimuli. Cells expressing this marker increased with age in some human and primate tissues. This marker enzyme, termed the senescence-associated beta-galactosidase (SA-Bgal), is expressed by replicatively senescent fibroblasts, epithelial and endothelial cells, and other cell types in culture. It is also expressed by fibroblasts induced to undergo a senescence arrest in response to DNA damage, oncogene expression, and agents that decondense chromatin. Fibroblasts and keratinocytes expressing SA-Bgal increase with age in human and monkey skin biopsies. In addition, retinal pigmented epithelial cells expressing this marker increase with age in the human retina. Together, these findings suggest that senescent cells, whether induced by cell division or other stimuli, progressively accumulate in at least some mammalian tissues.